摘要
目的:探讨NK细胞活化性受体NKG2D的结构与功能。方法:采用回顾性分析法系统归纳总结国内外近20年有关NKG2D结构与功能的研究资料。结果:NKG2D是表达于NK细胞表面的Ⅱ型膜蛋白受体,其基因定位于12p12. 3-p13. 1,含10个外显子和9个内含子。NKG2D单聚体蛋白质的三维结构含2个α螺旋,2个β片层,4个二硫键,主要依靠接头蛋白传递活化信号。NKG2D以同源二聚体形式结合DAP10,并使之磷酸化,然后与肿瘤表面的相应配体MICA、MICB、ULBPs结合,激活PI3K、PLCγ2、JNK-cJunN等信号通路,使NK细胞TNF-α、IFN-γ、颗粒酶释放分泌增加,Fas L、TRAIL表达上调,对肿瘤细胞发挥细胞毒性效应。结论:活化的NK细胞高表达NKG2D,而肿瘤细胞则高表达MICA、MICB、ULBPs,活化NK细胞表面的NKG2D与MICA、MICB、ULBPs结合,触发NK细胞释放多种细胞因子、分泌颗粒酶、表达Fas L、TRAIL,使靶细胞溶解,多途径发挥抗肿瘤作用。
Objective: To summarize the structure and function of NK cell activated receptor( NKG2 D). Methods: The data of NKG2 D and its function in activating NK cells in recent twenty years at home and abroad were systematically summarized by retrospective analysis. Results: NKG2 D was a type Ⅱ membrane protein receptor expressed on the surface of NK cells,which gene was located in 12 p12. 3-p13. 1,and consisted of 10 exons and 9 introns. The three-dimensional structure of NKG2 D monomeric protein contained two α-helices,two β-lamellae and four disulfide bonds,and mainly activates signal transduction by adaptor protein( DAP).NKG2 D was bound to DAP10 in homologous two dimer form and then could be phosphorylated. After NKG2 D on the surface of activated NK cells combine with the corresponding ligands( such as MICA,MICB,and ULBPs) on the surface of tumor cells,the signaling pathways of PI3 K,PLC gamma 2,JNK-cJunN and others should be activated,and the release and secretion of TNF-alpha,IFN-gamma,and granzyme from NK cells should be increased,and the expression of Fas L and TRAIL was up-regulated,which had multiple cytotoxic effects on hepatocellular carcinoma cells. Conclusion: Activated NK cells can express high level of NKG2 D. However,MICA,MICB and ULBPs all can be expressed on surface of tumor cells. NKG2 D on the surface of activated NK cells can combine with MICA,MICB and ULBPs,and triggers NK cells to release a variety of cytokines,secrete granzyme,express Fas L and TRAIL. It plays an important role in anti-tumor effects through multiple ways.
引文
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